A review by Twycross [1], identifies first-line anti-emetics and second-line drugs for nausea and vomiting. The first-line anti-emetic for gastritis, gastric stasis and functional bowel obstruction is metoclopramide. For most chemical causes of vomiting, haloperidol is prescribed. This, however, is not available to the nurse prescriber but metoclopramide may also be effective. Cyclizine should be prescribed for organic bowel obstruction, raised intracranial pressure and motion sickness. Second-line drugs include levomepromazine if first-line anti-emetics (in appropriate combination, dose and route) are inadequate. Domperidone is used to relieve nausea and vomiting, especially when associated with cytotoxic drug therapy. It does not readily cross the blood-brain barrier, and therefore has an advantage over metoclopramide of being less likely to cause central effects such as sedation.
 

Mode of action

Vomiting, or emesis, is the sudden and forceful oral expulsion of the stomach contents. It is a basic physiological protection mechanism that rids the gastrointestinal tract of noxious substances. Vomiting involves two functionally distinct medullary centres: the vomiting centre (VC) and the chemoreceptor trigger zone (CTZ). The act of vomiting is integrated by the VC and this orchestrates a complex series of events that results in nausea and vomiting. The CTZ is located on the floor of the fourth ventricle in the area postrema, where it is exposed to both blood and cerebrospinal fluid. This zone is considered to be outside the blood-brain barrier and is able to detect blood-borne drugs and toxins that are emetogenic. The VC may receive stimuli from the gastrointestinal tract and other organs, from the cerebral cortex, from the vestibular apparatus (responsible for motion sickness), and from the CTZ [2].

Metoclopramide and domperidone are dopamine receptor antagonists. They antagonise dopamine receptors in the CTZ that are involved in the vomiting reflex. In addition, they are both prokinetic anti-emetics as they increase the rate of gastric emptying and generally increase peristalsis. They also decrease the sensitivity of receptors in the pharynx and upper gut to noxious stimuli.

Cyclizine is an antihistamine and acts directly on H1-receptors in the vomiting centre by antagonising the action of histamine. Its effect appears to be on the vestibular pathway of the vomiting reflex and hence, it is particularly useful when motion causes symptoms of nausea and vomiting.

Levomepromazine antagonises dopamine receptors in the central nervous system, depressing the cerebral cortex, hypothalamus and limbic system. The clinical effects produced by this action include: a depressant action on conditioned responses and emotional responsiveness; a sedative action useful for the treatment of restlessness and confusion; an anti-emetic effect through blockade of the chemoreceptor trigger zone (CTZ), which is useful to treat vomiting; and antihistamine activity [3]. The World Health Organisation [4] suggest this drug is most useful for its sedative effect, in bed-bound patients during the last days of their life.

Contraindications

Metoclopramide should not be used in gastro-intestinal obstruction, perforation or haemorrhage.

Domperidone has no contraindications listed.

Cyclizine is contraindicated in hypersensitivity.

Levomepromazine is contra-indicated in hypersensitivity, comatose states, central nervous system (CNS) depression and phaeochromocytoma. It should be avoided in pregnancy.
 

Side-effects

Metoclopramide may produce extrapyramidal effects, hyperprolactinaemia, drowsiness, diarrhoea, depression, rashes, pruritus, and oedema.

Domperidone may also cause hyperprolactinaemia, galactorrhoea and gynaecomastia.

Cyclizine can cause drowsiness, dizziness, restlessness, insomnia, tachycardia, constipation, urinary retention, dry mouth and blurred vision.

Levomepromazine can cause agranulocytosis, leucopenia, haemolytic anaemia, jaundice, drowsiness, apathy, insomnia, depression, extrapyramidal symptoms, dry mouth, constipation, rashes, nasal congestion, blurred vision, hypotension, tachycardia and arrhythmias.

Nursing points

The most likely cause of the nausea and vomiting should be determined before an anti-emetic is prescribed. Correctable causes (e.g. constipation, drugs) should be managed or treated.

One third of patients may need more than one anti-emetic. The most appropriate first-line anti-emetic should be prescribed. However, if there is little or no benefit even though the dose has been optimised, an alternative first-line anti-emetic should be provided or a second-line anti-emetic added [1]. Due to the limited choice of anti-emetics available to the nurse prescriber, the nurse may need to refer the patient back to their physician.

The patient can be asked to keep a record of symptoms and response to the anti-emetic therapy.

References

1. Twycross R. (2000). Palliative care: anorexia, cachexia, nausea and vomiting. Medicine 28: 7-12.

2. Porth C. (1998). Pathophysiology: concepts of altered health states. 5th edition. Philadelphia: Lippincott.

3. Waller D. and Renwick A. (1994) – Principles of Medical Pharmacology. London: Balliere Tindall.

4. World Health Organisation (1998) - Symptom relief in terminal illness. Geneva: WHO.